Van Susteren was born in Appleton, Wisconsin. Her father, Urban Van Susteren, was of Dutch descent. Her mother, born Margery Conway, was a homemaker of Irish descent. Van Susteren's father was a longtime friend of future U.S. Senator Joseph McCarthy. McCarthy was best man at Greta Van Susteren's parents' wedding. Urban Van Susteren, an elected judge, served as a campaign strategist for McCarthy, although Urban later broke with him.
Van Susteren's sister, Lise, is a forensic psychiatrist in Bethesda, Maryland. In 2006, Lise was a candidate for the Democratic nomination for United States Senate. Her brother, Dirk Van Susteren, was a journalist and long-time editor of the Vermont Sunday magazine, jointly published, until folding in 2008, by the Rutland Herald and the Barre Montpelier Times Argus.
Van Susteren graduated from Xavier High School in Appleton in 1972 and the University of Wisconsin–Madison in 1976, where she studied geography and economics. She later earned a J.D. from Georgetown University Law Center in 1979 and prior to the start of her television work returned to Georgetown Law as an adjunct faculty member in addition to her full-time legal career. She was awarded an honorary doctor of laws degree from Stetson Law School.
During coverage of the O. J. Simpson murder trial, she appeared regularly on CNN as a legal analyst. This led to her stint as co-host of CNN's Burden of Proof and The Point.
Van Susteren made a special celebrity guest appearance on the Cartoon Network original series Space Ghost Coast to Coast in 1998.
In 2002, Van Susteren switched to the Fox News Channel after a highly publicized contract-bidding war. She hosted the current affairs show On the Record w/ Greta Van Susteren.
In 2012, an orphanage and school opened in Haiti called The Greta Home and Academy, which Greta and her husband helped found alongside Samaritan's Purse.
In 2014, Van Susteren criticized a Republican candidate for the U.S. Senate in Texas, Dwayne Stovall, who was challenging two-term incumbent John Cornyn in the primary election on March 4, 2014, after Stovall ran an advertisement calling Senate Minority Leader Mitch McConnell of Kentucky, Cornyn's superior in the Senate leadership, an ineffective "Beltway turtle." Until the controversial advertisement, the media had largely ignored Stovall's candidacy. Van Susteren called Stovall a "jerk" for running the ad: "You can be clever and funny in ads ... or you can be gratuitously insulting."
On September 6, 2016, she resigned from Fox News. She was not able to say goodbye on-air, as the network immediately filled the On the Record anchor spot with Brit Hume. Van Susteren, who said that Fox "has not felt like home to me for a few years," chose to take advantage of a clause in her contract that allowed her to resign from the network immediately: "The clause had a time limitation, meaning I could not wait."
In early 2017, Van Susteren signed on with NBC News to anchor the 6 p.m. ET program on its 24-hour cable news channel, MSNBC. The program, titled For the Record with Greta, launched on January 9, 2017. On June 29, 2017, according to Van Susteren on Twitter, she was "out at MSNBC" as her new program did not do well in ratings.
Van Susteren is on the Board of Directors at the National Institute for Civil Discourse (NICD). The institute was created at the University of Arizona in the aftermath of the 2011 Tucson shooting where 6 people were killed, and 13 others left wounded, including US Representative Gabrielle Giffords.
Van Susteren married tort lawyer John P. Coale in 1988. They are members of the Church of Scientology.
From August 2006 until January 2014, she was a co-owner of the Old Mill Inn, a restaurant in Mattituck, New York, on the North Fork of Long Island.